Knockdown of KDM1A suppresses tumour migration and invasion by epigenetically regulating the TIMP1/MMP9 pathway in papillary thyroid cancer.

Epigenetic dysregulation plays an important role in cancer. Histone demethylation is a well-known mechanism of epigenetic regulation that promotes or inhibits tumourigenesis in various malignant tumours. However, the pathogenic role of histone demethylation modifiers in papillary thyroid cancer (PTC), which has a high incidence of early lymphatic metastasis, is largely unknown. Here, we detected the expression of common histone demethylation modifiers and found that the histone H3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) demethylase KDM1A (or lysine demethylase 1A) is frequently overexpressed in PTC tissues and cell lines. High KDM1A expression correlated positively with age <55 years and lymph node metastasis in patients with PTC. Moreover, KDM1A was required for PTC cell migration and invasion. KDM1A knockdown inhibited the migration and invasive abilities of PTC cells both in vitro and in vivo. We also identified tissue inhibitor of metalloproteinase 1 (TIMP1) as a key KDM1A target gene. KDM1A activated matrix metalloproteinase 9 (MMP9) through epigenetic repression of TIMP1 expression by demethylating H3K4me2 at the TIMP1 promoter region. Rescue experiments clarified these findings. Altogether, we have uncovered a new mechanism of KDM1A repression of TIMP1 in PTC and suggest that KDM1A may be a promising therapeutic target in PTC.

Transfemoral versus Transapical Aortic Implantation for Aortic Stenosis Based on No Significant Difference in Logistic EuroSCORE: A Meta-Analysis.

Background Transcatheter aortic valve implantation (TAVI) has gained increasing acceptance for patients with severe aortic stenosis (AS). The present meta-analysis was performed to assess if the transapical (TA) approach has any benefit in reduction of mortality and complications relative to the transfemoral (TF) approach for patients with AS. Methods All relevant studies comparing TF-TAVI and TA-TAVI from January 2002 to November 2013 were retrieved from Medline and Embase databases. The relative risk (RR) and 95% confidence interval (CI) were used to evaluate the difference between two groups. Heterogeneity assumption was assessed by an I (2) test. The random-effect model or fixed-effect model was used to estimate summary effect based on I (2) test. Results Nine studies conformed to the predefined criteria, including 666 patients in the TF-TAVI group and 457 patients in the TA-TAVI group. No difference was found in all-cause mortality at 30 days and beyond 1 year between the two groups (30 days: 9.2% versus 11.4%; RR, 0.72; 95% CI, 0.47 to 1.11; p = 0.14 and beyond 1 year: RR, 0.96; 95% CI, 0.59 to 1.56; p = 0.86). There was a trend toward increased incidence of stroke in patients in the TF-TAVI group (4.7% versus 2.6%; RR, 1.64; 95% CI, 0.75 to 3.58; p = 0.21), and the incidence of vascular complication and postoperative heart block were significantly increased in patients having TF-TAVI (vascular complications: 14.7% versus 7.1%; RR, 2.04; 95% CI, 1.15 to 3.61; p = 0.01 and heart block: 13.4% versus 4.6%; RR, 2.53; 95% CI, 1.10 to 5.83; p = 0.03). Additionally, more patients in the TF-TAVI group required permanent pacemaker relative to the TA-TAVI group (10.8% versus 3.4%; RR, 2.74; 95% CI, 1.41 to 5.32; p = 0.003). Conclusions Among patients with AS with no significant difference in logistic EuroSCORE, TA-TAVI has a lower risk of vascular complication and postoperative heart block but a similar incidence of stroke and mortality compared with TF-TAVI. Accordingly, TA approach is a promising and feasible option for the patients with severe AS.